2019 ASCO Annual Meeting!
Session: Lung Cancer—Non-Small Cell Metastatic
Type: Poster Session
Time: Sunday June 2, 8:00 AM to 11:00 AM
Location: Hall A
Phase II randomized trial of afatinib with or without cetuximab as first-line treatment for EGFR mutated non-small cell lung cancer (NSCLC) patients (IFCT-1503 ACE-Lung).
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
Poster Board Number:
Poster Session (Board #402)
J Clin Oncol 37, 2019 (suppl; abstr 9079)
Author(s): Alexis B. Cortot, Anne Madroszyk, Etienne Giroux Leprieur, Olivier Molinier, Elisabeth A. Quoix, Henri Berard, Josianne Otto, Isabelle Rault, Judith Raimbourg, Jose Hureaux, Lionel Moreau, Didier Debieuvre, Hugues Morel, Marc G. Denis, Elodie Amour, Franck Morin, Denis Moro-Sibilot, Jacques Cadranel, French Cooperative Thoracic Intergroup (IFCT); Centre Hospitalier Regional Universitaire Lille, Lille, France; Institut Paoli-Calmettes, Marseille, France; APHP Hopital Ambroise Pare and Universite Paris-Saclay, Boulogne-Billancourt, France; Le Mans Regional Hospital, Le Mans, France; University Hospital of Strasbourg, Strasbourg, France; Hopital D'instruction Des Armes Sainte-Anne, Toulon, France; CLCC Lacassagne, Nice, France; Centre Hospitalier, Saint-Quentin, France; Centre Rene Gauducheau, Saint Herblain, France; Academic Hospital, Angers, France; Centre Hospitalier Pneumologie Colmar, Colmar, France; GHRMSA, Mulhouse, France; CHR, Orléans, France; Nantes University Hospital, Nantes, France; IFCT, Paris, France; Intergroupe Francophone de Cancérologie Thoracique, Paris, France; Grenoble University Hospital, Grenoble, France; Hôpital Tenon, AP-HP and Faculté de Médecine Pierre et Marie Curie, Université Paris VI, Paris, France
Background: First-line treatment of metastatic EGFR-mutated NSCLC relies on EGFR-TKIs. However, all patients (pts) eventually develop progression. Dual inhibition of EGFR with afatinib (A), an irreversible pan-erbB TKI, and cetuximab (C), an EGFR monoclonal antibody, has shown activity in EGFR-mutated pts with acquired resistance to TKIs, regardless of the T790M status. Methods: We conducted a phase II randomized trial in advanced NSCLC pts harboring an activating EGFR mutation, who had not received prior therapy. Pts were treated with A (40 mg/d) until progression alone or with C 500 mg/m² every 2 weeks during 6 months (mos) (beginning at D15 at 250 mg/m²). Primary endpoint was time-to-treatment failure (TTF) at 9 mos for pts with del19 and L858R mutations. Secondary endpoints include safety, progression-free survival (PFS), overall survival (OS). Prospective monitoring of the T790M mutation was performed on circulating tumoral DNA (ctDNA) by digital PCR. Results: Trial was stopped early due to futility analysis after 118 pts were enrolled (59 in each arm). Baseline characteristics were balanced between the 2 arms, and especially for the types of EGFR mutation (del19, 55.9 vs 50.8%; L858R, 39 vs 40.7%; others, 5.1 vs 8.5% in AC and A arms, respectively). Treatment-related AEs of any grades were similar, although there was an excess of grade 3 AEs in the AC arm (50 vs 37.3%), but no of grade 5. The excess in grade 3-5 AEs was essentially due to cutaneous (96.6 vs 81.4%), eyes (32.8 vs 27.1%), hematological (22.4 vs 15.3%) but not to digestive toxicities (89.7 vs 98.3%). Among the 117 pts included in the efficacy analysis, 9-months TTF was 63.3% (47.5-75.6) in arm A and 65.8% (50.1-77.66) in arm AC. Median TTF was 11.1 mos (8.3-not reached [NR]) and 10.8 mos (9.2-13.7) in arms A and AC, respectively. Median PFS was 11.1 mos (8.3-NR) and 12.8 mos (9.2-13.7), respectively. Median OS was 20.8 mos (17.5-NR) and NR (17-NR), respectively. Conclusions: Efficacy of AC was similar to that of A alone. These results don’t support further evaluation of this combination in this setting. Results of ctDNA monitoring will be reported during the meeting. Clinical trial information: NCT02716311